Anti-brain cholinergic auto antibodies from primary Sjögren syndrome sera modify simultaneously cerebral nitric oxide and prostaglandin biosynthesis

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• 作者：Betina Orman ; Leonor Sterin-Borda ; Alej ; ra De Couto Pita ; Silvia Reina ; Enri Borda
• 关键词：Antibodies ; Sjö ; gren syndrome ; mAChR ; Prostaglandin E₂ ; COX-1 mRNA ; COX-2 mRNA ; Nitric oxide synthase ; eNOS ; nNOS
• 刊名：International Immunopharmacology
• 出版年：2007
• 期刊代码：123_15675769
• 类别：med
• 出版时间：5 December 2007
• 卷：7
• 期：12
• 页码：1535-1543
• 文件大小：509 K

摘要

The presence of circulating antibodies from primary Sjögren Syndrome (pSS) patients enable to interact with rat cerebral frontal cortex by activating muscarinic acetylcholine receptors (mAChR). ELISA assay for PGE₂ generation, nitric oxide synthase (NOS) activity was measured in cerebral frontal cortex slices by production of [U–¹⁴C]-citruline and mRNA isolation/quantitative PCR for COX-1 and COX-2 gene expression were carried out. By ELISA assay, it was shown that IgG from pSS patients reacted to cerebral frontal cortex cell surface and with human M₁ and M₃ mAChR. Beside pSS IgG displayed an agonistic-like activity stimulating NOS activity and PGE₂ production associated with an increased COX-1 mRNA gene expression, without affecting COX-2 mRNA levels. Inhibition of phospholipase A₂ (PLA₂) and NOS prevented pSS IgG effects upon both PGE₂ production and COX-1 mRNA levels. The results support the notion that serum IgG auto antibodies in pSS patients target cerebral mAChR may have pathogenic role in immune neuroinflammation and on cognitive dysfunction present in pSS patients.